Clinical Reviews in Allergy & Immunology最新文献

{"title":"Fungal Infections in Disorders of Inborn Errors of Immunity.","authors":"Manpreet Dhaliwal, Vaishali Thakur, Adilia Warris, Gordon D Brown, Rakesh Kumar Pilania, Ivy M Dambuza","doi":"10.1007/s12016-026-09182-2","DOIUrl":"10.1007/s12016-026-09182-2","url":null,"abstract":"<p><p>Emerging infectious threats continually challenge the adaptability of the human immune system. Inborn errors of immunity (IEIs) provide a unique framework to dissect host-pathogen interactions, revealing how single-gene defects uncover critical pathways in antifungal defence. This review offers an overview of fungal immunity through the lens of IEIs, and integrates recent advances in innate fungal recognition, neutrophil and mononuclear phagocyte effector mechanisms, CARD9/NF-kB signalling, IL-17/IL-23 and IL-12/IFN-gamma cytokine axes, and transcription-factor defects that shape susceptibility to Candida, Aspergillus, Pneumocystis, Cryptococcus, dimorphic fungi and other moulds. We also discuss acquired phenocopies mediated by anti-cytokine autoantibodies, translate these mechanisms into clinical red flags and diagnostic algorithms, and discuss potential therapeutic strategies. Finally, we highlight how genetically defined IEIs can be used to study fungal-bacterial, fungal-mycobacterial and fungal-viral co-infections, revealing the hierarchy and plasticity of host defence in health and disease.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dual Roles of Innate Lymphoid Cells in Antibacterial Defense and Bacterial Immune Evasion.","authors":"Yuting Hu, Huaqing Liu, Qi Liu, Pengfei Sun, Changjiang Chen, Zhou Sha, Zhizeng Wang, Haibo Wu","doi":"10.1007/s12016-026-09183-1","DOIUrl":"https://doi.org/10.1007/s12016-026-09183-1","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) are critical regulators of early immune responses at mucosal barriers. As sentinels of the innate immune system, they rapidly detect infection-induced signals and initiate tissue-protective programs prior to the full activation of adaptive immunity. Emerging evidence shows that bacteria activate ILCs through multiple mechanisms, including direct recognition via pattern recognition receptors (PRRs), cytokine-mediated interactions with myeloid and epithelial cells, and metabolic and transcriptional modulation. Once activated, distinct ILC subsets coordinate antibacterial defense through cytotoxic activity and cytokine-driven regulation of macrophages, neutrophils, and epithelial cells. Notably, these pathways can be subverted by both pathogenic and commensal bacteria to manipulate ILC responses, enabling immune evasion and persistence, yet how bacterial signals are integrated and dynamically regulated by ILCs across tissues and disease contexts remains incompletely understood. Here, we synthesize recent progress in elucidating the molecular and cellular mechanisms underlying bacteria-ILC crosstalk, highlight emerging concepts and unresolved questions, and discuss how context-dependent ILC responses contribute to either host protection or disease progression. By integrating findings across infection models and mucosal environments, we propose a unifying framework for ILC-mediated antibacterial immunity and its dysregulation and highlight the therapeutic potential of targeting ILC-associated pathways as promising strategies for chronic and persistent bacterial infections.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Targeting of the Bradykinin B2 Receptor in Immunological and Vascular Diseases: Insights from Kinin Biology to Clinical Outcomes.","authors":"Marc A Riedl, Danny M Cohn, Markus Magerl, Henriette Farkas, Emel Aygören-Pürsün, Aleena Banerji, Jonathan A Bernstein, Alvin H Schmaier, Evangelia Pardali, Anne Lesage, Peng Lu, David E Newby","doi":"10.1007/s12016-026-09178-y","DOIUrl":"10.1007/s12016-026-09178-y","url":null,"abstract":"<p><p>Bradykinin is a nonapeptide of the kinin family with vasoactive and proinflammatory activities. While generation of kinins is mainly driven by activation of the contact system and plasma or tissue kallikreins, additional independent cascades contribute to their formation. Kinins mediate their effects through the constitutively expressed bradykinin B2 receptor and the inducible bradykinin B1 receptor. Bradykinin is the most studied kinin peptide mainly due to its potential role in the vascular system and exerts its effects mainly via the bradykinin B2 receptor. Kinins have been implicated in the pathogenesis of multiple types of angioedema as well as of various conditions, such as allergic mast cell-mediated skin diseases, cardiovascular and respiratory pathologies. This review summarizes our current knowledge of the biology, regulation, and functions of kinins and their receptors as well the emerging evidence on the various mechanisms involved in bradykinin formation and their relevance in disease pathogenesis. The review focuses on the clinical evidence on the roles of bradykinin and of the bradykinin B2 receptor in various conditions, and the potential to develop novel strategies targeting the bradykinin B2 receptor for management of bradykinin-mediated diseases.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-blocker Therapy in Cholinergic Urticaria, Adrenergic Urticaria and the Aquagenic Continuum Beta-Blocker Therapy in Chronic Inducible Urticaria.","authors":"Evelien M Hutten, Rick G Pleijhuis","doi":"10.1007/s12016-026-09175-1","DOIUrl":"10.1007/s12016-026-09175-1","url":null,"abstract":"<p><p>Chronic urticaria is a common skin disorder that substantially affects both daily functioning and quality of life. Among its subtypes, chronic inducible urticaria often presents with greater therapeutic challenges than chronic spontaneous urticaria. A comprehensive review of the available evidence indicates that β-blockers may offer a rapid-acting, well-tolerated, and effective treatment option for patients with specific subtypes of chronic inducible urticaria specifically cholinergic urticaria, adrenergic urticaria, and the aquagenic continuum. This approach introduces a readily available, non-parenteral, and cost-efficient therapeutic alternative that could also yield novel insights into the underlying pathophysiology of urticaria. In addition, this manuscript underscores the need to update current clinical guidelines by: (1) recognizing adrenergic urticaria as a distinct chronic inducible urticaria subtype; (2) broadening the conceptual framework for aquagenic-induced symptoms; and (3) standardizing intradermal test concentrations for adrenergic and cholinergic urticaria.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13328195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunopathogenesis and Cytokine Pathways in Reactive Infectious Mucocutaneous Eruption (RIME) in Pediatric Population: Infectious Triggers and Molecular Insights.","authors":"Filippos Filippatos, Konstantinos Kakleas, Athanasios Michos","doi":"10.1007/s12016-026-09177-z","DOIUrl":"10.1007/s12016-026-09177-z","url":null,"abstract":"<p><p>Reactive infectious mucocutaneous eruption (RIME) is increasingly recognized as a pediatric syndrome in which severe mucositis follows a recent infection and cutaneous involvement is usually limited. Although Mycoplasma pneumoniae remains the prototype trigger, influenza, SARS-CoV-2, adenovirus, respiratory syncytial virus, and other respiratory pathogens can produce a similar clinical phenotype. This narrative review summarizes pediatric RIME/MIRM literature and selected adult or comparator-disease evidence when direct pediatric data are unavailable, explicitly distinguishing direct RIME evidence from extrapolated mechanisms. This review synthesizes current evidence on the immunopathogenesis of RIME in children, with emphasis on how pathogen-specific factors intersect with innate and adaptive immune pathways to drive mucosal injury. We discuss the central roles of epithelial sensing, inflammasome activation, cytokine amplification, neutrophil recruitment, and T-cell polarization, and we relate these mechanisms to the severe oral, ocular, and anogenital disease that often defines pediatric presentations. We also integrate emerging proteomic data showing recurring molecular programs, including acute-phase and complement activation, neutrophil-associated epithelial injury, and interferon-inducible antiviral responses. In addition, we review the possible contribution of genetic susceptibility, especially variation in innate immune sensors and cytokine signaling pathways, to disease severity and recurrence. Finally, we address the main diagnostic challenges, histopathologic and imaging findings, differential diagnosis from Stevens-Johnson syndrome, erythema multiforme, and Kawasaki disease, and the implications of these insights for risk stratification and treatment. Taken together, current evidence supports RIME as a pathogen-triggered, mucosa-predominant inflammatory syndrome in which exaggerated host responses, rather than pathogen presence alone, shape the clinical phenotype.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13303683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148327169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tertiary Lymphoid Structure: A Potential Therapeutic Target Affecting Immune Response in Autoimmune Diseases.","authors":"Yanni Li, Rongrong Zheng, Xiaoxuan Wei, Hongyu Chu, Yiming Huo, Haonan Sun, Deman Li, Yuhan Du, Guixian Ji, Bangmao Wang, Lu Zhou","doi":"10.1007/s12016-026-09180-4","DOIUrl":"10.1007/s12016-026-09180-4","url":null,"abstract":"<p><p>Autoimmune diseases are characterized by the immune system's breakdown of self-tolerance, and manifest as either organ-specific or systemic conditions. Within the target tissues of diverse autoimmune diseases, tertiary lymphoid structures (TLSs) emerge under persistent inflammatory conditions. These pathological, ectopic lymphoid formations serve as sites for sustained antigen presentation, affinity maturation of antibodies, and proliferation /differentiation of B cells, thereby exacerbating local immune-mediated damage. Given their functional significance, TLSs represent promising candidates as diagnostic biomarkers and novel therapeutic targets for autoimmune pathologies. This review synthesizes the current knowledge on the pathological relevance of TLSs, the mechanisms driving their formation and the therapeutic targeting potential, aiming to deepen the understanding of how TLSs influence the immune microenvironment in autoimmune disease pathology.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropsychological Factors in Vitiligo: Mechanisms and Clinical Application.","authors":"Fei Fei Ren, Jia Zhou, Wei Zhang","doi":"10.1007/s12016-026-09176-0","DOIUrl":"10.1007/s12016-026-09176-0","url":null,"abstract":"<p><p>Vitiligo is a chronic autoimmune depigmenting disorder affecting 0.5%-2% of the global population, characterized by bidirectional interplay between psychological stress and disease progression, with accumulating evidence highlighting the central role and translational relevance of the neuro-endocrine-immune-cutaneous axis in its pathogenesis. Epidemiological data indicate over half of patients experience significant psychological stress prior to disease onset, while visible depigmentation markedly elevates the burden of depression and anxiety, establishing a self-amplifying pathogenic loop. Mechanistically, neural crest-derived melanocytes form functional \"neuro-pigment units\" with intraepidermal nerve endings, enabling bidirectional communication via neuropeptides including calcitonin gene-related peptide (CGRP) and substance P. Dynamic crosstalk among keratinocytes, sensory neurons, and melanocytes integrates neurotrophic and inflammatory signals to tightly regulate melanocyte survival and biological function. Sympathetic activation drives melanocyte injury via norepinephrine-mediated β2-adrenergic receptor signaling, while dopamine metabolites exacerbate apoptosis via the oxidative stress-Akt-Bad axis; context-dependent hypothalamic-pituitary-adrenal axis effects and light-melatonin-circadian clock disruption further promote immune dysregulation and melanocyte loss. Notably, neuromodulatory approaches like transcutaneous auricular vagus nerve stimulation show therapeutic promise by attenuating oxidative stress and limiting pathogenic CD8⁺ T-cell infiltration. These insights have fostered targeted strategies including CGRP receptor antagonists and dual antioxidant-neuroprotective natural compounds. Integrating neuroimmunological modulation with psychological and circadian interventions represents a promising precision medicine framework for vitiligo management.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Neuro Behcet's Disease Across North Africa: a Systematic Review and Meta Analysis.","authors":"Nabil Belfeki, Nouha Ghriss, Monia Smiti, Mohammed Amine Chami, Khalid Serraj, Aymane Bennani","doi":"10.1007/s12016-026-09173-3","DOIUrl":"10.1007/s12016-026-09173-3","url":null,"abstract":"<p><p>Data on neuro-Behçet's disease in North Africa remain limited and fragmented. We conducted a systematic review and meta-analysis to estimate the frequency of neurologic involvement in North African patients with Behçet's disease and to summarize the main clinical, cerebrospinal fluid, and imaging characteristics. PubMed, Scopus, and Web of Science databases were searched for studies reporting neuro-Behçet's disease in North Africa. Proportions were pooled using a random-effects meta-analysis model to estimate overall pooled proportions (OPP). Heterogeneity was assessed using I² statistics. The review protocol was registered in PROSPERO (CRD420261303759). Thirteen studies were included. Among 4262 patients with Behçet's disease, the pooled proportion of Neuro-Behçet's disease was 18.54% (95% CI 13.93% - 24.25%). The overall pooled proportions of parenchymal Neuro-Behçet's disease was 69.19% of cases (95% CI 58.79% - 77.96%). The main neurological symptoms were pyramidal signs (OPP 68.02%; 95% CI 35.27% - 89.25%), headaches (OPP 44.24%; 95% CI 23.16% - 67.63%), dysarthria/speech impairment (OPP 26.72%; 95% CI 13.49% - 46.02%), and cerebellar signs (OPP 23.60%; 95% CI 11.69% - 41.89%). Non-parenchymal involvement was mainly vascular, particularly cerebral venous thrombosis (OPP 25.92%; 95% CI 17.29% - 36.93%). Peripheral neuropathy was also reported (OPP 2.78%; 95% CI 1.22% - 6.24%). Neurological involvement in Behçet's disease is frequent in North Africa with a predominance of parenchymal forms. This first comprehensive meta-analysis benchmarks North African Neuro-Behçet's disease against global patterns and supports integrated clinical diagnosis over reliance on imaging alone.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life Gut Microbiota and Allergic Diseases: Immune Regulatory Mechanisms and Intervention Progress.","authors":"Lei Yu, Maolan Wu, Tingfan Leung, Xiangrong Zheng","doi":"10.1007/s12016-026-09174-2","DOIUrl":"10.1007/s12016-026-09174-2","url":null,"abstract":"<p><p>Over recent decades, the prevalence of allergic diseases has risen steadily, particularly among children, making these conditions a major global public health concern. Increasing evidence suggests that, in addition to genetic factors, gut microbiota dysbiosis is an important contributor to the development and progression of allergic diseases. The gut microbiota plays a critical role in host metabolism, maintenance of mucosal barrier integrity, and regulation of immune homeostasis, and is especially closely linked to immune system development and the establishment of immune tolerance in early life. Abnormalities in the composition and function of the gut microbiota may promote allergic susceptibility through multiple immunoregulatory pathways and contribute to the onset and progression of atopic dermatitis, allergic rhinitis, asthma, and other allergic diseases. This review focuses on the relationship between early-life gut microbiota and allergic diseases, summarizes the underlying immunoregulatory mechanisms, and discusses progress in microbiota-targeted interventions, with the aim of providing a reference for early prevention and precision intervention in allergic diseases.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Reprogramming and ILC2 Plasticity in Obesity-related Asthma.","authors":"Xiang Piao, Yingqi Hang, Li Bai, Mingyun Wu, Xiao Liu, Jianer Yu","doi":"10.1007/s12016-026-09169-z","DOIUrl":"10.1007/s12016-026-09169-z","url":null,"abstract":"<p><p>Obesity-related asthma is a major clinical challenge defined by its unique pathology and resistance to corticosteroids. Here, we reframe this disease through the lens of tissue-specific \"maladaptive plasticity\" of group 2 innate lymphoid cells (ILC2s). We propose a central dichotomy: in the obese lung, mechanical transduction synergizes with metabolic inflammation to induce a HIF-1α-mediated glycolytic shift in ILC2s. Conversely, in visceral adipose tissue (VAT), chronic metabolic stress drives ILC2 functional exhaustion, suppressing cytokine secretion. This pulmonary glycolytic shift fuels acetyl-CoA accumulation and subsequent epigenetic remodeling, which locks ILC2s into a pathogenic ILC1/ILC3-like phenotype, thereby driving the non-Th2 inflammation characteristic of obesity-related asthma. Furthermore, we describe how systemic metabolic stress propagates through the \"adipose-pulmonary\" and \"gut-pulmonary\" axes, which includes neutrophil extracellular traps (NETs) and glucocorticoid receptor isoform imbalances. Collectively, these pathological changes establish a refractory network of corticosteroid resistance, a primary factor contributing to treatment failure in obesity-related asthma. Based on these findings, we propose a novel therapeutic framework termed \"Metabolic Resuscitation\". This strategy shifts the focus from conventional immunosuppression to restoring cellular homeostasis by targeting key metabolic checkpoints and epigenetic drivers. This review provides a new mechanistic framework for understanding obesity-related asthma and offers a rationale for developing therapies to reverse treatment resistance.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":"69 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}